Myocardial Expression of PD-L1 as a Marker of Poor Prognosis in Immune Checkpoint Inhibitor–Associated Myocarditis

Figures

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  Figure 1. Myocardial PD-L1 Expression Representative images of myocardial hematoxylin and eosin (H&E) staining and PD-L1 immunostaining from a patient with immune checkpoint inhibitor–associated myocarditis. Arrowheads indicate PD-L1+ cardiomyocytes exhibiting either granular cytoplasmic staining or membranous staining patterns. Arrows indicate PD-L1+ immune cells with dense membranous and cytoplasmic staining.

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  Figure 2. Pathological Findings Stratified by MACE Occurrence Low-power field (LPF) and high-power field (HPF) images of hematoxylin and eosin (H&E) staining and immunohistochemical staining for PD-L1, CD3, CD4, CD8, and CD68. PD-L1, CD3, and CD68 were assessed by immunohistochemistry. CD3/CD4/DAPI and CD3/CD8/DAPI panels represent multiplex immunofluorescence staining of myocardial sections. Red boxes indicate the regions magnified in the corresponding HPF images. Myocardial samples from patients with major adverse cardiotoxic events (MACE) show prominent infiltration of CD3+ lymphocytes with CD8+ predominance and increased CD68+ macrophages, along with higher PD-L1 expression in myocardial tissue. In contrast, samples from patients without MACE show minimal inflammatory infiltrates and low PD-L1 expression.

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  Figure 3. Correlation Between PD-L1+ Cells and Myocardial Inflammatory Cells Scatter plots with linear regression lines showing the relationships between PD-L1+ cells and (A) CD3+ cells, (B) CD20+ cells, and (C) CD68+ cells in patients with immune checkpoint inhibitor–associated myocarditis. To accommodate values ≤1, all measurements were log-transformed after adding a constant of 1.

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  Central Illustration. Myocardial PD-L1 Expression and Inflammatory Burden in Immune Checkpoint Inhibitor–Associated Myocarditis High myocardial PD-L1 expression is associated with major adverse cardiotoxic events (MACE) and increased myocardial inflammatory burden in immune checkpoint inhibitor–associated myocarditis. The absolute risk of 30-day MACE was significantly higher in the high PD-L1 (PD-L1 ≥8%) group than in the low PD-L1 (PD-L1 <8%) group (n = 5 of 7 [71.4%] vs n = 1 of 13 [7.7%]; P = 0.007). PD-L1 positivity correlated with CD3+ T cell and CD68+ macrophage infiltration. These findings suggest that myocardial PD-L1 staining may help identify patients at higher risk and support earlier intervention and closer monitoring. H&E = hematoxylin and eosin.